This is an application for integrated pre- and post-doctoral training support that will bring together cutting edge clinical strategies with experimental investigations on the mechanisms and biology of skeletal tissue repair and regeneration. The proposal is based in the skeletal biology program centered in the Department of Anatomy &Cell Biology at Rush University Medical Center in partnership with the Department of Orthopedic Surgery (which includes one of the premier clinical orthopedic groups in the country as well as an outstanding group of basic scientists). Faculty from two other clinical departments at Rush (Section of Rheumatology from the Department of Internal Medicine and the Department of Plastics &Reconstructive Surgery) are expected to participate as mentors or co-mentors. The objective of the proposed program is to provide education, training and research opportunities to doctoral students, postdoctoral fellows and medical students interested in academic careers in the multi-disciplinary area of skeletal biology. The program will emphasize mechanisms of skeletal repair and regeneration in order to direct training to basic biological research foundations for orthopedics, rheumatology and craniofacial surgery. We are requesting support for 3 graduate students, 2 post-doctoral fellows and 2 short-term research trainees. In addition to traditional PhD students and MD/PhD students, a special effort will be made to recruit students seeking combined MD/MS degrees. Although our MD/MS program is relatively new, all of the students who have participated are on a very encouraging track of becoming physician-scientists. We think this track is particularly important for students interested in surgical careers because of the extremely long clinical training requirements. Thus, emphasis on the MD/MS (as opposed to the MD/PhD) still permits a meaningful intense research experience, but adds only one year (as opposed to three years) to the entire training regimen. At the post-doctoral level, we plan to pay special attention to the recruitment of MDs and MD/PhDs. The short-term research trainee mechanism will be used as a way to provide an introduction to research for medical students who are still considering the MD/MS or MD/PhD option. We are taking this strategy to help bolster the number of physician-scientists in orthopedic skeletal biology. Relevance: This grant will help train scientists to improve healing of damaged bone and joints. Current orthopedic procedures are successful, but we hope to improve outcomes through a better understanding of the underlying pathologies and mechanisms the body uses to repair itself. Eventually, treatments will rely more on the body's natural ability at self-renewal and less on the use of artificial materials.